We hope to estimate quantitatively the pathways by which ethanol is oxidized, primarily in the liver, to acetaldehyde, and the subsequent metabolism of this. Isotopic techniques using specifically tritiated and deuterated compounds will be employed. The rate-limiting transfer of cytosolic reducing equivalents produced in the alcohol dehydrogenase reaction to the mitochondria by systems such as the gamma-glycerophosphate shuttle or the malate-aspartate cycle will be determined. We have designed a rigorous test of the role of blood acetaldehyde concentration during ethanol uptake in the predisposition of animals to the use of ethanol. We hope to develop optimum procedures to accelerate ethanol utilization in isolated liver cells and to determine the effectiveness and safety of these methods in the whole animal.